Drugs that target KIT and PDGFRa have transformed the way we treat GIST.  While these drugs may be very effective initially, most patients eventually become resistant to them. They develop additional or ‘secondary’ mutations in an area known as the ‘activation loop,’ which keep the tumor in a persistently activated state. Once this happens, drugs like Gleevec, Sutent, and Stivarga cannot gain access to the binding pocket in sufficient quantity to effectively control tumor growth.
Two new drugs, BLU-285 and DCC-2618, are under development to specifically target GISTs harboring activation loop mutations.  Both drugs have demonstrated pre-clinical activity against primary and secondary mutations, including and most importantly, the PDGFRa D842V mutation.  Both BLU-285 and DCC-2618 have been moved from the dose-escalation phase to the dose expansion phase of study. A presentation of these findings was given by Dr. Michael Heinrich at the 2017 GISTS Summit and recent trial data can be viewed here.


Is a novel, oral, investigational drug focusing on inhibition of PDGFRα D842V and KIT Exon 17 mutants.  The shape of the BLU-285 molecule is designed to better enable binding to the ATP pocket.  A phase III trial comparing BLU-285 against Regorafenib as a third line of defence is planned.  A press release by Blueprint Pharmaceuticals can be found here.   


 A paper titled “A precision therapy against cancers driven by KIT/PDGFRA mutations” was published online in Science Translational Medicine on November 1, 2017.

“In June 2017, BLU-285 received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. Previously, the FDA granted orphan drug designation to BLU-285 for the treatment of GIST and SM. The FDA also granted fast track designation to BLU-285 for the treatment of patients with unresectable or metastatic GIST that progressed following treatment with imatinib and a second tyrosine kinase inhibitor and for the treatment of patients with unresectable or metastatic GIST who have the PDGFRα D842V mutation regardless of prior therapy.”



Is a novel, oral, investigational potent pan-KIT and PDGFRα kinase inhibitor with activity across a broad range of tyrosine kinase inhibitor mutations. These include primary KIT exon’s 9,11, or 17 as well as secondary KIT mutations across exon’s 13, 14, 17, and 18.  The shape of the DCC-2618 molecule is designed to restore accessibility to the binding pocket when it is blocked by the presence of a loop activation mutation.

A new Phase III Clinical Trial for patients who have been treated with imatinib, sunitinib, and regorafenib was posted to clinicaltrials.gov in November 2017.

Please see the following link for the latest information:


Phase 3 Study of DCC-2618 vs Placebo in Advanced GIST Patients Who Have Been Treated With Prior Anticancer Therapies – Full Text View – ClinicalTrials.gov

This is a 2‑arm, randomized, placebo-controlled, double‑blind, international, multicenter study comparing the efficacy of Deciphera’s DCC-2618 to placebo in patients who have received treatment with prior anticancer therapies.


An article about DCC-2618 in the European Society for Clinical Oncology journal can be viewed here.  You can also  view the clinical trial protocol by clicking here.